Human gingival mesenchymal stem cell-derived exosomes cross-regulate the Wnt/beta-catenin and NF-kappa B signalling pathways in the periodontal inflammation microenvironment

Aim: To examine the immunomodulatory effect of exosomes originating from gingival mesenchymal stem cells (GMSC-Exo) on periodontal bone regeneration and its role in the regulation of the nuclear-factor kappaB (NF-kappa B) and Wnt/beta-catenin pathways in the periodontal inflammatory microenvironment.Materials and Methods: First, periodontal ligament stem cells (PDLSCs) were treated with GMSC-Exo or Porphyromonas gingivalis-derived lipopolysaccharide (P.g-LPS) in vitro. Quantitative real-time PCR (qRT-PCR) and western blot were carried out to detect the expressions of osteogenic differentiation-related factors in cells. Further, PDLSCs were treated with P.g-LPS or inhibitors. The expression of NF-kappa B pathway-related factors as well as of Wnt/beta-catenin pathway-related factors were detected by qRT-PCR and western blot.Results: GMSC-Exo treatment promoted the expression of osteogenic differentiation-related factors within PDLSCs in both normal and inflammatory environments. Further investigations showed that GMSC-Exo could also inhibit the P.g-LPS-induced activation of the NF-kappa B pathway, leading to the up-regulation of the Wnt/beta-catenin pathway. When the Wnt/beta-catenin signalling was blocked, the inhibitory effect of GMSC-Exo on the NF-kappa B pathway was abolished.Conclusions: GMSC-Exo could promote the osteogenic differentiation of PDLSCs. There could be mutually exclusive regulatory roles between the NF-kappa B and Wnt/beta-catenin signalling pathways in a periodontal inflammatory environment. GMSC-Exo exhibited an effective cross-regulation ability for both pathways.